Incoming links: De novo DNA synthesis
Using de novo DNA synthesis to synthesize entire Chromosomes.
Using de novo DNA synthesis to synthesize a genes to later insert somewhere.
Note that this is a specific application of de novo DNA synthesis, e.g. polymerase chain reaction primers is another major application that does not imply creating genes.
"De novo" means "starting from scratch", that is: you type the desired sequence into a computer, and the synthesize it.
The "de novo" part is important, because it distinguishes this from the already well solved problem of duplicating DNA from an existing DNA template, which is what all our cells do daily, and which can already be done very efficiently in vitro with polymerase chain reaction.
Many startup companies are attempting to create more efficient de novo synthesis methods:
Notably, the dream of most of those companies is to have a machine that sits on a lab bench, which synthesises whatever you want.
TODO current de novo synthesis costs/time to delivery after ordering a custom sequence.
The initial main applications are likely going to be:but the real pipe dream is building and bootstraping entire artificial chromosomes
- polymerase chain reaction primers (determine which region will be amplified
- creating a custom sequence to be inserted in a plasmid, i.e. artificial gene synthesis
News coverage:
- 2023-03 twitter.com/sethbannon/status/1633848116154880001
AnsaBio created the world's longest DNA oligo produced using de novo synthesis! 1,005 bases! 99.9% stepwise yield
- 2020-10-05 www.nature.com/articles/s41587-020-0695-9 "Enzymatic DNA synthesis enters new phase"
Nuclera eDNA enzymatic de novo DNA synthesis explanatory animation (2021)
Source. The video shows nicely how Nuclera's enzymatic DNA synthesis works:- they provide blocked nucleotides of a single type
- add them with the enzyme. They use a werid DNA polymerase called terminal deoxynucleotidyl transferase that adds a base at a time to a single stranded DNA strand rather than copying from a template
- wash everything
- do deblocking reaction
- and then repeat until done
As of 2019, the silicon industry is ending, and molecular biology technology is one of the most promising and growing field of engineering.
42 years of microprocessor trend data by Karl Rupp
. Source. Only transistor count increases, which also pushes core counts up. But what you gonna do when atomic limits are reached? The separation between two silicon atoms is 0.23nm and 2019 technology is at 5nm scale.Such advances could one day lead to both biological super-AGI and immortality.
Ciro Santilli is especially excited about DNA-related technologies, because DNA is the centerpiece of biology, and it is programmable.
First, during the 2000's, the cost of DNA sequencing fell to about 1000 USD per genome in the end of the 2010's: Figure 2. "Cost per genome vs Moore's law from 2000 to 2019", largely due to "Illumina's" technology.
The medical consequences of this revolution are still trickling down towards medical applications of 2019, inevitably, but somewhat slowly due to tight privacy control of medical records.
Ciro Santilli predicts that when the 100 dollar mark is reached, every person of the First world will have their genome sequenced, and then medical applications will be closer at hand than ever.
But even 100 dollars is not enough. Sequencing power is like computing power: humankind can never have enough. Sequencing is not a one per person thing. For example, as of 2019 tumors are already being sequenced to help understand and treat them, and scientists/doctors will sequence as many tumor cells as budget allows.
Then, in the 2010's, CRISPR/Cas9 gene editing started opening up the way to actually modifying the genome that we could now see through sequencing.
What's next?
Ciro believes that the next step in the revolution could be could be: de novo DNA synthesis.
This technology could be the key to the one of the ultimate dream of biologists: cheap programmable biology with push-button organism bootstrap!
Just imagine this: at the comfort of your own garage, you take some model organism of interest, maybe start humble with Escherichia coli. Then you modify its DNA to your liking, and upload it to a 3D printer sized machine on your workbench, which automatically synthesizes the DNA, and injects into a bootstrapped cell.
You then make experiments to check if the modified cell achieves your desired new properties, e.g. production of some protein, and if not reiterate, just like a software engineer.
Of course, even if we were able to do the bootstrap, the debugging process then becomes key, as visibility is the key limitation of biology, maybe we need other cheap technologies to come in at that point.
This a place point we see the beauty of evolution the brightest: evolution does not require observability. But it also implies that if your changes to the organism make it less fit, then your mutation will also likely be lost. This has to be one of the considerations done when designing your organism.
Other cool topic include:
- computational biology: simulations of cell metabolism, protein and small molecule, including computational protein folding and chemical reactions. This is basically the simulation part of omics.If we could only simulate those, we would basically "solve molecular biology". Just imagine, instead of experimenting for a hole year, the 2021 Nobel Prize in Physiology and Medicine could have been won from a few hours on a supercomputer to determine which protein had the desired properties, using just DNA sequencing as a starting point!
- microscopy: crystallography, cryoEM
- analytical chemistry: mass spectroscopy, single cell analysis (Single-cell RNA sequencing)
It's weird, cells feel a lot like embedded systems: small, complex, hard to observe, and profound.
Ciro is sad that by the time he dies, humanity won't have understood the human brain, maybe not even a measly Escherichia coli... Heck, even key molecular biology events are not yet fully understood, see e.g. transcription regulation.
One of the most exciting aspects of molecular biology technologies is their relatively low entry cost, compared for example to other areas such as fusion energy and quantum computing.
Basically a synonym for doing a large chunk of de novo DNA synthesis.
Man-made virus!
TODO: if we had cheap de novo DNA synthesis, how hard would it be to bootstrap a virus culture from that? github.com/cirosantilli/cirosantilli.github.io/issues/60
Is it easy to transfect a cell with the synthesized DNA, and get it to generate full infectious viral particles?
If so, then de novo DNA synthesis would be very similar to 3D printed guns: en.wikipedia.org/wiki/3D_printed_firearms.
It might already be possible to order dissimulated sequences online: